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J M Vose

Publications and source records attributed to J M Vose.

At least 55 records · Page 3Linked to original sources
PubMed1998

High incidence of relapse after autologous stem-cell transplantation for B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.

BACKGROUND: High-dose therapy followed by autologous stem-cell transplantation (autoSCT) induces complete remissions in the majority of patients with advanced B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma (B-CLL). However, the long-term utility of this therapy for B-CLL is unknown. PATIENTS AND METHODS: Sixteen previously treated patients with B-CLL were transplanted using autologous blood (n = 13) or bone marrow (n = 3). The median age of the patients was 49 f1p4s (range 44-60 years), and the median number of prior chemotherapy regimens was two. Patients were eligible for transplantation if they had chemosensitive disease and no morphologic evidence of malignant cells in the graft. Preparative regimens included cyclophosphamide and total-body-irradiation, with or without cytarabine, or BEAC. RESULTS: All patients engrafted and achieved a complete remission posttransplant. Ten patients were alive at a median of 41 months (range 22-125 months), and five were disease-free. Eight patients have relapsed and six have died (three from progressive malignancy). The projected three-year overall survival, failure-free survival and relapse rates were 68%, 37%, and 56%, respectively. CONCLUSIONS: AutoSCT for advanced B-CLL is associated with a high relapse rate. Whether this therapy can prolong life or produce cures is uncertain.

Adult↗
PubMed1998

Lymphocyte reconstitution after allogeneic blood stem cell transplantation for hematologic malignancies.

Forty-one patients were studied at set times after allogeneic blood stem cell transplantation (alloBSCT) for recovery of lymphocyte numbers and function. Cells were mobilized with G-CSF from HLA-matched related donors and cryopreserved. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate; G-CSF was administered post-transplant. Median time to absolute lymphocyte count (ALC) >500/microl was 17 days vs 41 and 49 days in historical alloBMT patients with G-CSF (n = 23) or no cytokine (n = 29) post-transplant, respectively (P < 0.0001). CD4/CD8+ ratio was 1.9 on day 28 after alloBSCT, then gradually declined to 0.8 at 1 year due to more rapid CD8+ cell recovery. Mean phytohemagglutinin-induced T cell responses were lower than normal on day +28 (P < 0.05), then tended to recover towards normal values. Natural-killer cytotoxicity remained low from day +28 to 1 year post-alloBSCT, but considerable lymphokine-activated killer cytotoxicity was induced from cells already obtained on day +28. Faster lymphocyte recovery correlated with better survival in alloBSCT patients (median follow-up 287 days, P = 0.002), ALC recovery was not affected by acute GVHD, CMV infections or doses of infused cells. ALC recovery did not correlate with survival in either historical alloBMT group. These data suggest that after alloBSCT lymphocyte reconstitution is faster than after alloBMT, and that quicker lymphocyte recovery predicts better survival in the alloBSCT setting.

Adult↗
PubMed1998

Epstein-Barr virus-associated lymphoproliferative disorder after autologous bone marrow transplantation: report of two cases.

Epstein-Barr virus-associated lymphoproliferative disorders have been frequently reported as a complication of solid organ and allogeneic bone marrow transplantation. Their occurrence is rare after autologous bone marrow transplantation (BMT) with only five published reports in the literature. We report two cases of post-transplant lymphoproliferative disorder occurring after autologous BMT for Hodgkin's disease and non-Hodgkin's lymphoma. Post-transplant lymphoproliferative disorders can occur after autologous BMT and should be included in the differential diagnosis of patients with persistent fever, adenopathy or pulmonary infiltrates.

Adult↗
PubMed1998

High-dose chemotherapy and hematopoietic stem cell transplantation for relapsed or refractory diffuse large-cell non-Hodgkin's lymphoma.

The use of high-dose chemotherapy and transplantation for chemotherapy sensitive relapsed diffuse large-cell non-Hodgkin's lymphoma is now the gold standard for patients who are candidates for such therapy. Recent data also demonstrates the relative effectiveness of this approach for patients who are induction failures but are continuing to respond to conventional therapy at the time of transplantation. Newer approaches such as the use of novel agents to modify the transplant regimen, newer cytokines, or alternative sources of hematopoietic stem cells need to be tested in order to improve the outcome in patients with chemotherapy resistant disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Effect of follicularity on autologous transplantation for large-cell non-Hodgkin's lymphoma.

PURPOSE: This study evaluated the outcomes of patients who received high-dose chemotherapy (HDC) and autologous hematopoietic stem-cell transplantation (ASCT) for large-cell non-Hodgkin's lymphoma (NHL) and the effect of a follicular versus a diffuse histology. PATIENTS AND METHODS: The prognostic factors in 289 patients who underwent HDC and ASCT for large-cell NHL between May 1983 and December 1996 were analyzed. RESULTS: With a median follow-up duration of 24 months for surviving patients (range, 3 to 131 months), 112 of 289 (39%) were alive and 82 of 289 (28%) were failure-free. In a multivariate analysis, the factors associated with a poorer failure-free survival (FFS) included a lactic dehydrogenase (LDH) level greater than normal (P < .0001), three or more prior chemotherapy regimens received (P < .01), a mass > or = 10 cm at transplant (P < .01), and diffuse histology at the time of transplant (P = .026). Patients who received HDC and ASCT for large-cell NHL in the good-prognosis category (normal LDH, < three prior chemotherapy regimens, no large mass, and not chemotherapy-resistant) had a 5-year survival rate of 45%. Within the good-prognosis group, patients with diffuse large-cell NHL had a 5-year survival rate of 42% compared with 58% for patients with follicular large-cell (FLC) lymphoma (P = .05). CONCLUSION: Good-prognosis patients with FLC histology who receive HDC and ASCT have an improved survival compared with good-prognosis patients with a diffuse large-cell histology.

Adolescent↗
PubMed1998

Lymphoma cells associated with bone marrow stromal cells in culture exhibit altered growth and survival.

The detection of clonal populations of lymphoma cells in histologically negative bone marrow using culture techniques is a predictor of poor outcome for patients undergoing high dose therapy and autologous transplantation. In positive cultures, lymphoma cells were observed as outgrowths in association with adherent stromal cells, whilst only stromal cells were observed in negative long-term cultures. This study developed an experimental model to further study the interactions occurring between lymphoma cells and stromal cells. Using random dot graticule analysis, 86% and 74%, respectively, of patient lymphoma cells grew in association with stromal cells in leukapheresis and bone marrow harvest cultures with the formation of cobblestone areas at sites of interaction between lymphoma cells and stromal cells. Secondary cultures showed that individual stromal cells were able to support the growth of a small number of lymphoma cells. Coculture of the human lymphoma cell lines with a murine bone marrow stromal cell line, MS-5 also resulted in the formation of cobblestone areas, which corresponded with the suppression of nonadherent cell production by the lymphoma cell lines. Upon interacting with MS-5 cells, the lymphoma cell lines formed pseudopodia and underwent pleiomorphic nuclear changes. Contiguous linear homotypic associations between lymphoma cells were evident, as opposed to focal contacts occurring in the heterotypic interactions between lymphoma cells and MS-5 cells. An increasing proportion of supernatant lymphoma cells underwent apoptosis as time in culture increased. These results demonstrate that bone marrow stromal cells alter the pattern of growth of lymphoma cells and may have an important role in the maintenance of occult lymphoma by inhibiting apoptosis.

Apoptosis↗
PubMed1998

Current approaches to the management of non-Hodgkin's lymphoma.

Non-Hodgkin's lymphoma (NHL) is a complex malignancy with many different clinical presentations, histologies, and varied treatment options depending on the histologic type and other prognostic factors. This article focuses on the major histologic subtypes of NHL with discussion of the natural history of each and information on various treatment options.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Rapid immunologic reconstitution following transplantation with mobilized peripheral blood stem cells as compared to bone marrow.

A majority of patients with intermediate or high-grade non-Hodgkin's lymphoma (NHL) who are treated with high-dose chemotherapy (HDT) and hematopoietic stem cell transplantation subsequently relapse. Until recently, transplantation was associated with high morbidity and mortality and the focus was on improving the safety of this procedure. However, the use of growth factors and other supportive measures has successfully reduced treatment mortality to less than 5%. Therefore, new strategies need to be developed to eliminate the growth of any occult tumor cells reinfused with the stem cell products and the tumor cells remaining in the patient. One approach is to improve the immune function of the patients by a more rapid immune reconstitution and augmentation of effector cell function. We report studies comparing immune recovery following HDT and autologous peripheral stem cell transplantation (PSCT) as compared to autologous bone marrow transplantation (ABMT). These studies examined patients with intermediate and high-grade non-Hodgkin's lymphoma (NHL) who were treated with HDT and PSCT (n = 56) or ABMT (n = 60). The PSCT patients had a significantly faster recovery of circulating monocytes (CD14+ cells), natural killer ((NK) CD56+) cells, T helper (CD4+) cells, TCR gamma/delta cells, and naive T lymphocytes (CD45RA+). Following ABMT there was a significantly more rapid increase in the frequency of T suppressor/effector (CD8+) cells, B (CD19+) cells, CD34+ cells, polymorphonuclear leukocytes (PMN) and memory T lymphocytes (CD45RO+). The CD4:CD8 and CD45RA:CD45RO ratios were consistently higher in the PSCT group as compared to ABMT suggesting an improved ratio of T helper to T effector/suppressor cells and naive T cells. The differences in cellular phenotype translated into improved T cell function (PHA mitogenesis) and T cell help (pokeweed mitogenesis). In addition, there as an accelerated reconstitution of NK cell activity following PSCT as compared to ABMT. The more rapid reconstitution of NK and T cells in patients rescued with PSCT as compared to ABMT may contribute to an improved clinical outcome. Further, patients receiving a PSCT may be more responsive to adjuvant immunotherapy following transplantation.

Adult↗
PubMed1997

High-dose therapy with autologous hematopoietic rescue for follicular low-grade non-Hodgkin's lymphoma.

PURPOSE: This study evaluated the results of high-dose therapy followed by autologous bone marrow or peripheral-blood stem-cell transplantation for patients with follicular low-grade non-Hodgkin's lymphoma. PATIENTS AND METHODS: We performed a retrospective review of 100 patients undergoing autologous transplantation for follicular low-grade lymphoma between April 22, 1983 and December 31, 1993. RESULTS: Sixty-seven patients remained alive and 48 were failure-free. The median follow-up duration of surviving patients was 2.6 years (range, 1.0 to 11.7). There were eight (8%) deaths within 100 days of transplantation. Six additional patients died of nonrelapse causes up to 912 days after transplantation. Overall survival at 4 years was estimated to be 65% (95% confidence interval [CI], 54% to 75%) and failure-free survival was estimated to be 44% (95% CI, 33% to 55%). There was no definite evidence of a plateau in the failure-free survival curve. The only factor significantly associated with overall survival and failure-free survival was the number of chemotherapy regimen received before transplantation. No significant differences in outcome were observed between patients with follicular small cleaved-cell lymphoma and follicular mixed lymphoma, or between patients who received peripheral-blood stem-cell transplants and unpurged autologous bone marrow transplants. CONCLUSION: Prolonged failure-free survival is possible following high-dose therapy and autologous hematopoietic rescue for follicular low-grade lymphoma. It is unclear whether patients are cured with this therapy or if survival is prolonged.

Adult↗
PubMed1997

Allogeneic-blood stem-cell collection following mobilization with low-dose granulocyte colony-stimulating factor.

PURPOSE: The optimal dose of granulocyte colony-stimulating factor (G-CSF) for mobilization of allogeneic-blood stem cells (AlloBSC) has yet to be determined. As part of a prospective trial, 41 related human leukocyte antigen (HLA)-matched donors had blood cells mobilized with G-CSF at 5 micrograms/kg/d by subcutaneous administration. The purpose of this trial was to monitor adverse effects during G-CSF administration and stem-cell collection, to determine the optimal timing for stem-cell collection, and to determine the cellular composition of stem-cell products following G-CSF administration. PATIENTS AND METHODS: The median donor age was 42 years. Apheresis began on day 4 of G-CSF administration. At least three daily 12-L apheresis collections were performed on each donor. A minimum of 1.0 x 10(6) CD34+ cells/kg (recipient weight) and 8.0 x 10(8) mononuclear cells/kg were collected from each donor. All collections were cryopreserved in 5% dimethyl sulfoxide and 6% hydroxyethyl starch. RESULTS: Toxicities associated with G-CSF administration and the apheresis process included myalgias/arthralgias (83%), headache (44%), fever (27%), and chills (22%). The median baseline platelet count of 242 x 10(4)/ mL decreased to 221, 155, and 119 x 10(6)/mL on days 4, 5, and 6 of G-CSF administration, respectively. Median numbers of CD34+ cells in collections 1, 2, and 3 were 1.99, 2.52, and 3.13 x 10(6)/kg, respectively. The percentage and total number of CD4+, CD8+, and CD56+/CD3- cells remained relatively constant during the three collections. Median total numbers of cells were as follows: CD34+, 7.73 x 10(6)/kg; and lymphocytes, 6.93 x 10(8)/kg. CONCLUSION: Relatively low doses of G-CSF can mobilize sufficient numbers of AlloBSC safely and efficiently.

Adult↗
PubMed1997

Hematopoietic recovery after allogeneic blood stem-cell transplantation compared with bone marrow transplantation in patients with hematologic malignancies.

PURPOSE: To compare hematopoietic recovery, duration of hospitalization, and 100-day survival in patients who received allogeneic-blood stem cells (BSC) or conventional allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: From December 1994 to August 1995, 21 patients participated in a phase II study of allogeneic BSC transplantation. Cells mobilized with granulocyte colony-stimulating factor (G-CSF; 5 micrograms/kg/ d) were collected from human leukocyte antigen (HLA)-matched related donors and cryopreserved. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. G-CSF (10 micrograms/kg/d) was administered posttransplant. The outcomes were compared with 22 identically treated historical patients who received allogeneic BMT. RESULTS: The median infused CD34+ cell and granulocyte-macrophage colony-forming unit (CFU-GM) content were 7.73 x 10(4)/kg and 41.6 x 10(4)/kg, respectively. The median time to a neutrophil count greater than 500/ microL was 11 days after BSC and 16.5 days after BMT (P = .0003). A trend toward faster platelet and RBC recovery after BSC was observed. BSC patients received fewer platelet transfusions: 10 versus 19 (P = .015). The median length of hospitalization was shorter after BSC transplantation: 25 versus 31.5 days (P = .0243). The 100-day survival rates were similar: 83% after BSC and 75% after BMT (P = .3585). The incidence of acute GVHD grade II to IV was 57% and 45% for BSC and BMT, respectively (P = .4654). CONCLUSION: In comparison to BMT, allogeneic BSC transplantation may result in faster hematopoietic recovery, shorter hospital stay, and similar early survival. Whether allogeneic BSC are superior to bone marrow needs to be determined in randomized trials.

Adult↗
PubMed1997

Granulocyte-macrophage colony-stimulating factor/interleukin-3 fusion protein versus granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for non-Hodgkin's lymphoma: results of a randomized double-blind trial.

PURPOSE: A phase III trial to compare PIXY321 with granulocyte-macrophage colony-stimulating factor (GM-CSF) following high-dose therapy and autologous bone marrow transplant (ABMT) was conducted to evaluate the time to hematopoietic recovery. PATIENTS AND METHODS: One hundred seventy-seven patients with non-Hodgkin's lymphoma (NHL) receiving ABMT were randomized to receive either PIXY321 750 micrograms/m2/d divided into two subcutaneous (SC) doses or GM-CSF 250 micrograms/m2/d as a 2-hour intravenous (IV) infusion starting on day 0 post-ABMT for a maximum of 28 days. RESULTS: The median time to reach an absolute neutrophil count (ANC) > or = 500/microL in the PIXY321 group was 17 days versus 19 days in the GM-CSF group (P = .07) and the median time to reach platelet transfusion independence in the PIXY321 group was 25 days versus 23 days in the GM-CSF group (P = .30). The toxicity profiles of the two agents appeared to be equivalent with the exception of more patients in the PIXY321 group with a rash (64%) compared with the GM-CSF group (48%) (P = .028). A logistic regression model identified the use of a non-total-body irradiation (TBI) regimen and/or receipt of unpurged marrow and a body-surface area greater than 2.0 m2 as predictive of faster neutrophil engraftment, and those three factors, as well as the receipt of < or = two prior chemotherapy regimens as predictive for rapid platelet engraftment. CONCLUSION: There was a trend toward a slight improvement in neutrophil engraftment post-ABMT with the PIXY321 administered by an SC route compared with GM-CSF administered by an IV route. However, no differences could be identified between the two agents with respect to the time to platelet transfusion independence. Patient, regimen, and graft characteristics were most predictive of the engraftment tempo.

Adolescent↗
PubMed1996

Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma.

Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.

Adolescent↗
PubMed1996

Classification and clinical course of low-grade non-Hodgkin's lymphomas with overview of therapy.

Low-grade non-Hodgkin's lymphoma (NHL) presents a formidable treatment challenge to oncologists. This review evaluates the various methods of disease and patient management. The natural history of various subtypes of low-grade NHL and the classification according to the National Cancer Institute Working Formulation are discussed in this review. Additionally, the various therapies in use; radiotherapy alone and combined with chemotherapy, chemotherapy with single alkylating agents such as chlorambucil and combination therapies, autologous and allogenic bone marrow transplantation, and therapy with purine analogs, such as chlorodeoxyadenosine and fludarabine. Patient survival in various studies using these treatment modalities are discussed. Treatment options need to be combined with the use of prognostic models, such as the International Index for optimal care of this difficult-to-treat group of patients.

Humans↗
PubMed1996

High-dose chemotherapy followed by autologous hematopoietic rescue for Hodgkin's disease patients following first relapse after chemotherapy.

BACKGROUND: The best results of conventional-dose salvage chemotherapy for Hodgkin's disease have been reported after first relapse. We evaluated the results of high-dose chemotherapy and autologous hematopoietic rescue for Hodgkin's disease patients who had relapsed from an initial chemotherapy-induced complete remission. PATIENTS AND METHODS: Eighty-five patients received high-dose cyclophosphamide, carmustine, and etoposide (CBV) followed by autologous bone marrow or peripheral blood stem cell transplantation. RESULTS: Actuarial survival at five years was 51%, and failure-free survival was 40%. Failure-free survival at five years was 90% for patients who received no conventional-dose salvage chemotherapy prior to CBV. Failure-free survival of patients treated initially with a four-drug regimen was not significantly different than patients treated with seven/eight-drug regimens. CONCLUSION: These results appear to be better than those reported for conventional-dose salvage chemotherapy. High-dose therapy followed by autologous bone marrow or peripheral blood stem cell transplantation should be considered for any patient with relapsed Hodgkin's disease, regardless of the length of initial remission, or type of initial chemotherapy. Certain patients, especially those with minimal disease, may benefit by proceeding directly to transplantation after relapse, without first receiving conventional-dose salvage chemotherapy.

Adolescent↗
PubMed1996

Hodgkin's disease following solid organ transplantation.

BACKGROUND: The incidence of second malignancies is markedly increased following transplantation of solid organs. However, the development of Hodgkin's disease has been described relatively infrequently in this setting, and there is little clinical information on these patients and few details on management. PATIENTS AND METHODS: We have reviewed the pathologic specimens and clinical history of four patients who developed Hodgkin's disease following transplantation of solid organs. RESULTS: Hodgkin's disease appeared 26-68 months following transplantation of the kidney (2 cases), liver, and heart. Three cases demonstrated evidence of Epstein-Barr virus (EBV) in Reed-Sternberg cells. One case appears to have arisen after a previous EBV-driven polymorphous lymphoproliferation. Hodgkin's disease was localized in three cases and disseminated in one. All patients achieved remission with standard therapy and continue in remission between 9 and 61 months after therapy. Graft function was preserved in all patients. CONCLUSION: Hodgkin's disease occurring in the post-transplantation period should probably be treated like Hodgkin's disease in non-immunosuppressed patients. Prolonged disease-free survival is possible and function of the transplanted organ can be preserved.

Adult↗
PubMed1996

Estimates of net photosynthetic parameters for twelve tree species in mature forests of the southern Appalachians.

Leaf gas exchange, temperature, and incident radiation were measured in situ for 20 mature trees of 12 deciduous species spanning a range of heights from 7.9 to 30.1 m and growing in the southern Appalachian Mountains. Air temperature, water vapor pressure, total radiation, photosynthetically active radiation, and carbon dioxide concentration were also measured. Estimated mean, light-saturated net assimilation rates ( micro mol m(-2) s(-1)) were: Quercus coccinea Muenchh. (10.3), Q. prinus L. (9.9), Q. rubra L. (8.9), Betula lenta L. (8.1), Liriodendron tulipifera L. (7.9), Q. alba L. (7.6), Carya glabra Mill. (7.2), Acer rubrum L. (5.6), Nyssa sylvatica Marsh. (3.9), Cornus florida L. (3.5), and Acer pensylvanicum L. (1.7). There were significant differences in both net assimilation rates and quantum yield efficiencies between species, with the understory species C. florida and A. pensylvanicum exhibiting lower net assimilation rates at saturation and higher estimated quantum yield efficiencies than the other species. Average temperature and light decreased from the canopy top to bottom, whereas ambient CO(2) concentration increased, and vapor pressure and vapor pressure deficits were inconsistent. We observed curvilinear effects of temperature and vapor pressure deficit on net assimilation response to light, and these effects varied by species. Errors in predicted net assimilation ranged from 1 to 3 micro mol m(-2) s(-1) under the environmental conditions prevailing during the study.

Journal Article↗